Denture adhesive

ABSTRACT

Denture adhesive compositions with sufficient initial adhesion to the gums that build up enough cohesive strength upon hydration with saliva to withstand the stresses occurring during food mastication and cushions the gums from contact with the denture during chewing. The adhesive comprises a mixed partial salt of an amino ethyl ethylene urea substituted polyalkylvinylether/maleic acid copolymer wherein the cations of the salt are selected from the group consisting of zinc, calcium, magnesium, strontium, zirconium, sodium, and potassium.

FIELD OF THE INVENTION

This invention relates to denture adhesives and to methods for makingand using denture adhesives. In particular, this invention relates to anamino ethyl ethylene urea-substituted mixed partial salt of a copolymerof a polyalkyl vinyl ether and maleic acid, (PVE/MA) as a new dentureadhesive active.

BACKGROUND OF THE INVENTION

Ordinary removable dentures and dental plates function as a substitutefor all or part of missing teeth ordinarily found in the mouth. Whiledentures are usually carefully fitted for the user, the fit can changeover time, causing discomfort and slippage. In order to alleviate thediscomfort and to control the slippage, a denture adhesive may beapplied to the denture. The denture adhesive acts both as an adherentand as a gasket or cushion between the dentures and the gums of thedenture wearer. Denture adhesives are known and can be in the form ofcreams, liquids, powders, and liners, either extruded or with anon-adhesive self-supporting layer.

Denture adhesives are designed to provide a diverse range of seeminglycontradictory properties in an extraordinarily complex environment,i.e., the human mouth. Denture adhesives must develop a quick tack uponcontact with the oral mucosa to prevent the denture from coming loose;they must also develop cohesive strength quickly when hydrated withmoisture or saliva. They must also hold the denture in place for aperiod of time, which may be as long as 12 to 16 hours. Dentureadhesives should only need to be applied once per day and should benontoxic and organoleptically acceptable. They must not be easily washedout, i.e., the adhesive must resist degradation under extremeenvironmental changes occurring in the oral cavity during the course ofdaily activities, e.g., drinking hot or cold beverages. But, dentureadhesives must also easily release from the dentures and oral mucosaafter use.

Early denture adhesives contained finely ground particles of naturalgums that expanded when wet with water to become a viscous gel, whichacted as a cushion and an adherent between the dental plate and the gumtissue. These early denture adhesives have been supplanted by polymericdenture adhesives.

Several attempts have been made to fashion a denture adhesive usingvarious polymer salts. One preferred polymer from the field is a mixedpartial salt of a copolymer of maleic acid and alkyl vinyl ether, soldunder the GANTREZ® trade name. This class of polymers was described as apossible denture adhesive in Germann, et al. U.S. Pat. No. 3,003,988,which issued more than 30 years ago.

That patent describes synthetic, water sensitized but water insoluble,materials comprising mixed partial salts of lower alkyl vinylether-maleic acid copolymers for stabilizing dentures. The saltsmentioned in the patent are a mixture of (a) calcium and (b) sodium, orpotassium or quaternary ammonium compounds in a 1:1 to 5:1 molar ratio.The calcium hydroxide and monovalent cation hydroxides are added to anaqueous dispersion of the acid copolymer to form a mixed salt.

The use of this class of materials has been described in a variety ofother patents. Examples include U.S. Pat. Nos. 5,830,933; 4,980,391;4,373,036; 5,006,571; 4,521,551; 3,868,432 and European Published PatentApplication No. 406,643.

In order to provide additional adhesive and cohesive properties todenture adhesives made from GANTREZ® polymers, one approach has been tomanipulate the salt form of the copolymer. Examples can be found in WO92/22280, WO 92/10988, WO 92/10987, and WO 92/10986.

One approach is found in U.S. Pat. No. 4,758,630 to Shah et al., issuedJul. 19, 1988, which is directed to denture adhesives having mixedpartial salts of zinc and strontium.

Another approach is reported in U.S. Pat. No. 5,073,604 to Holeva etal., issued Dec. 17, 1991, which is directed to a denture adhesive madefrom a partial salt of a GANTREZ® copolymer, wherein the cations arezinc ions in combination with calcium or strontium ions in combinationwith with calcium, and optionally containing sodium cations.

U.S. Pat. No. 5,298,534 to Prosise et al., issued Mar. 29, 1994, reportsusing GANTREZ® salts of calcium, sodium, strontium, zinc, magnesium andpotassium with boron cross-linked guar gum and an oil base as a carrier.The preferred mixed salt is a Ca/Na mixed salt. The guar gum is“critical” to the asserted extended holding power and viscosity buildingproperties.

Another approach has been to employ an adhesion adjuvant in theformulation or converting the copolymer into a terpolymer, and examplesof these approaches can be found in U.S. Pat. Nos. 3,736,274, 5,037,924and 5,093,387.

Despite the efforts which have been put into improving the properties ofmaleic anhydride/alkyl vinyl ether type polymers and their salts asuseful denture adhesive actives, these formulations do not provide thefull desired measure of adhesion, cohesion, agreeable taste andresistance to washout from beneath the denture. Therefore, there existsa need for improved denture adhesive formulations.

SUMMARY OF THE INVENTION

The principal object of the present invention therefore, is to provide anew and improved denture adhesive composition having an unusually strongaffinity for oral tissues and for the acrylic denture, and builds up acohesive strength for good hold characteristics when hydrated withmoisture or saliva so as to be able to resist stresses such as thosethat occur upon mastication.

Another object of the invention is to provide an adhesive in which theimproved adhesive retains its adhesive properties for prolonged periodsof time and resists wash out. Still another object of the invention isto provide an adhesive that cushions the gums from the denture stressesthat develop during the chewing of food.

Additional objects and advantages of the invention will be set forth inpart in the description that follows, and in part will be obvious fromthis description, or may be learned by practice of the invention. Theobjects and advantages of the invention may be realized and attained bymeans of the instrumentalities and combinations particularly pointed outin the appended claims.

To achieve the foregoing objects and in accordance with the purpose ofthe invention, as embodied and broadly described herein, the inventionprovides a denture adhesive comprising a mixed metal salt containingsodium, and/or calcium, and/or zinc and/or strontium and/or magnesium,and/or potassium cations, of an AEEU-substituted-partial salt ofpolyalkyl vinyl ether/maleic acid, copolymer.

To further achieve the foregoing objects and in accordance with thepurpose of the invention, the invention further provides a method forsecuring a removable dental device in the mouth comprising applying adenture adhesive comprising a mixed metal, AEEU-substituted-partial saltof polyalkylvinyl ether, maleic acid, copolymer. The function of theAEEU substituent in this salt copolymer is to confer on this saltcopolymer the property of specific adhesion to the oral tissues and toan acrylic denture.

DETAILED DESCRIPTION OF THE INVENTION BRIEF DESCRIPTION OF THE DRAWINGS

While this specification concludes with claims particularly pointing outand distinctly claiming that which is regarded as the present invention,the objects and advantages of this invention may be more readilyascertained from the following description of a preferred embodimentwhen read in conjunction with the accompanying drawings.

FIG. 1 is a chart depicting a dislodge force profile comparison of threedenture adhesives creams containing varying adhesive components: (1)Gantrez Salt 418, (2) AEEU substituted at a level of 0.3 molarsubstitution to Salt 418 and (3) AEEU substituted Salt 418 with theaddition of 0.5% S-97 Gantrez acid.

The polymer salts of the present invention are the mixed partial saltsof a C₁-C₄ alkyl vinyl ether maleic acid copolymer. Methyl vinylether/maleic anhydride (MVE/MA) which has a specific viscosity largerthan 1.2 in methyl ethyl ketone at 25° C., is the preferred startingmaterial copolymer. The anhydride copolymer is mixed with the AEEU atroom temperature and then converted to an amide at elevatedtemperatures, hydrolized to the acid and then neutralized with theappropriate cations. Most preferably, copolymers are selected from thecopolymers set forth in U.S. Pat. No. 5,525,652, the disclosure of whichis incorporated herein by reference. While the copolymers of thatinvention are the preferred copolymers, this invention is not limited tothe use of those copolymers.

Suitable metal salt combinations include, but are not limited to, amixed salt of sodium/magnesium/zinc, a mixed salt of magnesium/zinc, amixed salt of zinc/calcium, a mixed salt of calcium/sodium, a mixed saltof calcium/potassium, a mixed salt of calcium/strontium, a mixed salt ofcalcium/zirconium, a mixed salt of magnesium/strontium, a mixed salt ofmagnesium/zirconium, a mixed salt of sodium/strontium, a mixed salt ofsodium/zirconium, a mixed salt of zinc/strontium, a mixed salt ofzinc/zirconium and a mixed salt of magnesium/sodium and the like.

The degree of substitution limits for alkyl vinyl ether/maleic acid(MVE/MA) partial salts of the invention are: (a) from about 5% to about55% magnesium, more preferably from about 15% to about 45% magnesium,and most preferably from about 20% to about 40% magnesium; (b) fromabout 5% to about 65% zinc, more preferably from about 10% to about 60%zinc, and most preferably from about 15% to about 55% zinc; and (c) fromabout 0% to about 40% sodium, preferably from about 0% to about 35%sodium, and most preferably from about 0% to about 30% sodium.

The polymer salt is prepared by the partial neutralization of an aqueouspremix of AEEU and the alkylvinylether/maleic acid or anhydridecopolymer with the oxides and hydroxides of the alkali salts, forexample, calcium, strontium, potassium, magnesium, zinc, sodium, andzirconium. When the salt is prepared, the metal compounds used, reactwith the carboxylic acid groups on the copolymer and neutralize them.Preferably less than 100% of the carboxylic acid groups on the copolymerchain are neutralized. More preferably, the metal compounds neutralizefrom the 20% to about 95% of the carboxylic acid groups of the copolymerand most preferably from about 30% to about 85% of the carboxylic acidgroups.

In choosing the alkaline, inorganic metal compound used to neutralizethe carboxylic acid groups, the anion portion of the compound isrestricted, and is preferably an oxide, hydroxide, or carbonate. Ingeneral, the oxides or hydroxides are preferred because of their ease ofhandling, availability and the generally innocuous nature of theby-products formed in their reaction with carboxylic acids.

To make the salt of the invention, an aqueous dispersion of themethylvinylether/maleic anhydride Copolymer and an aqueous solution ofAEEU are first blended together at 25° C. and held at 25° C. for 20minutes with continuous mixing, after that 20 minutes an aqueousdispersion of the metal oxides and or hydroxides is added to the AEEU,anhydride, water mixture and then the temperature is gradually raised.The dispersion of metal compounds and the AEEU-anhydride copolymerdispersion are combined and allowed to react at an elevated temperature,preferably between 50° C. and 90° C. The product salt formed is dried,either in a tray or drum drier and preferably milled to less than about100 mesh, then dispersed in a pharmacologically acceptable carrier toform the denture adhesive of this invention using techniques well knownin the art.

MVE/MA copolymer is available from ISP Corporation in New Jersey, underthe trade name GANTREZ®. The polymer is available in a GANTREZ-S serieswhich is methyl vinyl ether/maleic acid and in GANTREZ AN series, whichis methyl vinyl ether/maleic anhydride.

AEEU, which has the general structure:

is available from King Industries, Norwalk, Conn. under the tradenameK-Flex XM-3323.

The denture adhesive composition of the present invention contains adenture adhesive effective amount of the AEEU-substituted dentureadhesive copolymer salt in a pharmacologically acceptable carrier. TheAEEU-substituted denture adhesive copolymer salt usually comprises fromabout 15% to about 55% by weight of the denture adhesive composition.Preferably it is about 25% to about 35% by weight of the dentureadhesive cream composition, and most preferably from about 27% to about33% by weight of the composition in a cream formulation and about 45% toabout 55% by weight in a powder formulation.

Denture adhesives of this invention can be formulated by conventionaltechniques, in the form of a powder, a liquid, a cream, or a liner. Thecompositions also contain other active and non-active ingredients.

When the denture adhesive is formulated into a liner, the liner may be ahot-melt extruded film as described in for example, U.S. Pat. No.RE33,093 to Schiraldi et al. and U.S. Pat. No. 6,375,963 to Repka etal., both incorporated by reference herein. In another embodiment, thedenture adhesive may be in the form of a liner, wherein the dentureadhesive composition is applied to a non-adhesive-self-supporting layer,as described in, for example, U.S. Pat. Nos. 4,632,880 and 4,503,116, toLapidus and U.S. Pat. No. 5,880,172 to Rajaiah et al., and U.S. Pat. No.5,872,160 to Liang, all of which are incorporated herein by reference.

The active ingredient in the adhesive is the inventive metal partialsalt of the AEEU-substituted MVE/MA copolymer. The AEEU degree ofsubstitution should be between 0.05% and 0.5%, but preferably between0.1% and 0.4%. Without being bound by theory, it is believed that thestrong hydrogen bonding between the ureido group in the AEEU moleculeand the peptide linkages in the oral tissues and the carbonyl groups inthe acrylic polymer of the denture is responsible for the strongspecific adhesion of this AEEU substituted copolymer to the gums andacrylic denture.

In addition, the adhesive agent sodium carboxymethyl cellulose gum maybe added as an active ingredient. Non-active ingredients may includepetrolatum, mineral oil, flavors, colors, preservatives, thickeners anda non-toxic anti-caking agent such as fumed silica.

In addition to the denture adhesive, the composition contains apharmacologically acceptable carrier. The pharmacologically acceptablecarrier contains conventional materials and if desired, may contain anyadditional adhesive adjuvants that have been used conventionally in theart.

For instance, the carrier may contain a carboxymethyl cellulose gum thatis used for sensitizing the adhesive to moisture. When present, thecellulose gum preferably comprises from about 10% to about 38% by weightof the denture adhesive cream composition, more preferably from about15% to about 33% and most preferably from about 20% to about 28% of thecomposition for a cream formula. In a powder formula, the cellulose gumpreferably comprises from about 45% to about 55% of the composition. Ifincluded in the inventive composition, the cellulose gum should bepresent as the full or partial alkali metal salt, preferably a sodiumsalt.

Non-active ingredients that may be present in the carrier portion of thedenture adhesive composition include thickening agents such aspetrolatum and waxes; mineral oil to provide lubricity; flavors such assynthetic flavor oils and/or oils derived from plants and fruits; colorssuitable for food, drug and cosmetic use and known as FD&C colors;preservatives such as the parabens, benzoic acid, benzoates and thelike; viscosity modifiers; and non-toxic and anti-caking agents such assilica, magnesium stearate and talc.

In a cream formulation, mineral oil preferably comprises from about 12%to about 17% by weight of the composition. Petrolatum is used as thethickening agent in the cream formulation by retarding the separation ofthe formula vehicle from the rest of the cream formula during productstorage, and it preferably comprises from about 20% to about 50%,preferably from about 25% to about 45% by weight of the adhesive creamcomposition.

An illustrative composition of a denture adhesive cream formulationusing an AEEU-substituted GANTREZ salt of the invention follows: CreamWeight Cream Weight Ingredient % % AEEU-substituted   30%   30% (Ca/Na0.37%) GANTREZ ® Salt CMC   24%   24% Flavorant  0.32% Petrolatum 26.5%27.18% Mineral Oil   18%   18% Preservative Colorants Gantrez Acid   1%Fumed Silica  0.5%  0.5%

An illustrative composition of a denture adhesive specially formulatedto be compatible with a tube container and a powder formulation, using aCa/Na 0.37% AEEU-MVE/MA salt of this invention follows: PowderIngredient Weight % AEEU-substituted 49.84% (Ca/Na 0.37%) GANTREZ ® saltCMC 49.84% Flavorant  0.32% Petrolatum Mineral Oil PreservativeColorants Fumed Silica AC Polyethylene 6AThe following examples are to be construed as merely illustrative andnot a limitation on the scope of the invention in any way.

EXAMPLE 1

A partial sodium, calcium AEEU salt of poly(methyl vinyl ether-co-maleicacid) (MVE/MA) was prepared by adding 3.6 g. of AEEU to 9750 g. of waterat room temperature with stirring followed by adding 726.2 g. ofpoly(methyl vinyl ether-co-maleic anhydride) to the aqueous AEEUsolution after the solution had mixed for 10 minutes. The poly(methylvinyl ether-comaleic anhydride) was mixed in the AEEU solution at roomtemperature for 20 minutes. Next 251.6 g. of calcium hydroxide wascharged into the polymeric anhydride/AEEU solution at room temperature.Next a pre-mix of 18.6 g. of sodium hydroxide dissolved in 2750 g. ofroom temperature water was added to the calcium hydroxide/polymethylvinyl ether maleic anhydride/AEEU mix with stirring. Next thetemperature of this mixture was raised gradually to 65° C. with stirringand then the temperature was held at 65° C. for an additional 30 minutesafter which the product was discharged, dried in a forced air ovenovernight at 65° C. and then the product was milled. Product assayshowed that this partial salt contained 0.37% AEEU, 11.6% calcium, and0.91% sodium and 9.2% water.

The AEEU substituted partial sodium, calcium salt of poly(methyl vinylether maleic acid) prepared as described above was used to make alaboratory batch of denture adhesive paste (Formula B below). A controlbatch of adhesive was also made using unsubstituted calcium, sodiumMVE/MA salt as the active (Formula A below). A third batch of adhesivepaste was made with 0.5% GANTREZ Acid activator and AEEU substitutedPVM/MA salt according to Formula C presented below: FORMULA C AEEU SALTFORMULA FORMULA WITH 0.5% A B GANTREZ ® ACID CONTROL CONTROL FORMULACalcium, Sodium 30.0 MVE/MA Salt AEEU Substituted 30.0 30.0 Calcium,Sodium MVE/MA Salt Sodium 24.0 24.0 24.0 Carboxymethyl- cellulosePetrolatum 27.5 27.5 27.5 Mineral Oil 18.0 18.0 18.0 Fumed Silica  0.5 0.5  0.5 GANTREZ ® Acid  0.5

Paste adhesive formulas A, B, and C were tested for hang time (a measureof creep resistance), dislodge force, and subjective test performanceaccording to the attached SOP's for these test procedures. The resultsof these tests are shown in FIG. 1.

The results indicate that formula C tested significantly higher fordislodge force than the control formula Both Formulas B and C testedsignificantly higher for hang time than Formula A. These resultsunexpectedly indicate that only a relatively small amount of AEEU isneeded to produce a significant change in adhesive performance.

All publications, including, but not limited to, patents and patentapplications cited in this specification, are herein incorporated byreference as if each individual publication were specifically andindividually indicated to be incorporated by reference herein as thoughfully set forth.

The above description fully discloses the invention including preferredembodiments thereof. Modifications and improvements of the embodimentsspecifically disclosed herein are within the scope of the followingclaims. Without further elaboration it is believed that one skilled inthe art can, given the preceding description, utilize the presentinvention to its fullest extent. Therefore any examples are to beconstrued as merely illustrative and not a limitation on the scope ofthe present invention in any way. The embodiments of the invention inwhich an exclusive property or privilege is claimed are defined asfollows.

1. A denture adhesive composition comprising a denture adhesiveeffective amount of a denture adhesive salt which is an amino ethylethylene urea-substituted mixed partial salt of a copolymer of apolyalkyl vinyl ether and maleic acid, in a pharmaceutically acceptablecarrier, wherein the cations of the salt are selected from, zinc,sodium, calcium, potassium, magnesium, strontium, zirconium orcombinations thereof.
 2. The composition according to claim 1, whereinthe cations of the partial salt are a combination of sodium, magnesiumand zinc.
 3. The composition according to claim 1, wherein the cationsof the partial salt are a combination of magnesium and zinc.
 4. Thecomposition according to claim 1, wherein the cations of the partialsalt are a combination of zinc and calcium.
 5. The composition accordingto claim 1, wherein the cations of the partial salt are a combination ofcalcium and sodium.
 6. The composition according to claim 1, wherein thealkyl moiety is methyl.
 7. The composition according to claim 1, whereinthe composition is in the form of a cream.
 8. The composition accordingto claim 6, wherein the AEEU-substituted denture adhesive copolymer saltcomprises about 15-55% by weight of the total composition.
 9. Thecomposition according to claim 1, wherein the composition is in the formof a powder.
 10. The composition according to claim 1, wherein thecomposition is in the form of a liner.
 11. The composition according toclaim 10, wherein the liner is in the form of a hot-melt extruded liner.12. The composition according to claim 10, wherein the liner is in theform of a non-adhesive self-supporting layer.
 13. The compositionaccording to claim 1, further comprising a polyalkylvinylether/maleicacid activator.
 14. The composition according to claim 13, where in thepolyalkylvinylether/maleic acid activator is present from about 0.1% toabout 10% by weight of the composition.
 15. A compound which is a mixedpartial salt of an amino ethyl ethylene urea substitutedpolyalkylvinylether/maleic acid copolymer.
 16. The compound according toclaim 15, wherein the acid copolymer is neutralized with a cationselected from the group consisting of zinc, sodium, calcium, potassium,magnesium, zirconium, and strontium, or combinations thereof.